Glycopolymers/PEI complexes as serum-tolerant vectors for enhanced gene delivery to hepatocytes. (1st February 2019)

• Record Type: Journal Article
• Authors: Zhao, Liman; Li, Yanchun; Pei, Danfeng; Huang, Qingrong; Zhang, Hongwei; Yang, Zechuan; Li, Fan; Shi, Tongfei
• Is Part Of: Carbohydrate polymers. Volume 205(2019)
• Page Start: 167
• Page End: 175
• Publication Date: 2019-02-01
• Subjects: Galactose -- PEI -- Gene delivery -- Serum-tolerant -- Hepatocyte; Polysaccharides -- Periodicals; Polysaccharides -- Periodicals; Polysaccharides -- Périodiques; Electronic journals; 547.78
• DOI: 10.1016/j.carbpol.2018.10.036
• Languages: English
• ISSNs: 0144-8617

Abstract

Graphical abstract: Highlights: Comb-shaped cationic glycopolymers (DDrLs) was synthesized by atomic transfer radical polymerization. DDrLs/PEI as pDNA vector exhibited a remarkable serum-tolerant capability. The optimum efficiency of DDrLs/PEI can reach two orders of magnitude higher than that of PEI alone at 30% serum. DDrLs/PEI complexes with galactose enhanced pDNA delivery to hepatocytes. DDrLs/PEI/pDNA complexes had lower cytotoxicity than PEI/pDNA. Abstract: Serum stability is a crucial factor for ideal polymeric gene vectors. In this work, a series of serum-tolerant and low-toxicity glycopolymers/poly(ethyleneimine) (PEI) complexes were designed for gene delivery. Atomic transfer radical polymerization (ATRP) was used to synthesize the comb-shaped random copolymers dextran- g -poly(2-dimethylaminoethyl methacrylate- co -2-lactobionamidoethyl methacrylate) (DDrL). Then DDrLs/PEI were investigated for their use as plasmid DNA (pDNA) vectors, which can completely condense the pDNA into nanoparticles. The DDrLs/PEI/pDNA complexes in serum-containing media showed better stability than PEI/pDNA complexes. in vitro gene transfection studies showed that DDrLs/PEI exhibited a remarkable transfection efficiency enhancement in the presence of serum compared to that in serum-free conditions. Moreover, the transfection level of DDrLs/PEI were two orders of magnitude higher than that of PEI alone in the presence of 30% serum. DDrLs/PEI complexes with galactose enhanced pDNA delivery to hepatocytes, with higher protein expression in ASGPr-presenting HepG2 than in HeLa cells, which lack the receptor. All of the DDrLs/PEI/pDNA complexes had lower cytotoxicity than PEI/pDNA.